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Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.

Giotis ES, Rothwell L, Scott A, Hu T, Talbot R, Todd D, Burt DW, Glass EJ, Kaiser P - PLoS ONE (2015)

Bottom Line: The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR.Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow.From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Agri-Food and Biosciences Institute, Belfast, United Kingdom; Queen's University Belfast, Belfast, United Kingdom; The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
Chicken Anaemia Virus (CAV) is an economically important virus that targets lymphoid and erythroblastoid progenitor cells leading to immunosuppression. This study aimed to investigate the interplay between viral infection and the host's immune response to better understand the pathways that lead to CAV-induced immunosuppression. To mimic vertical transmission of CAV in the absence of maternally-derived antibody, day-old chicks were infected and their responses measured at various time-points post-infection by qRT-PCR and gene expression microarrays. The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR. The global gene expression profiles of mock-infected (control) and CAV-infected chickens at 14 dpi were also compared using a chicken immune-related 5K microarray. Although in the thymus there was evidence of induction of an innate immune response following CAV infection, this was limited in magnitude. There was little evidence of a Th1 adaptive immune response in any lymphoid tissue, as would normally be expected in response to viral infection. Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow. From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis. Expression levels of a number of adaptor proteins, such as src-like adaptor protein (SLA), a negative regulator of T-cell receptor signalling and the transcription factor Special AT-rich Binding Protein 1 (SATB1), were significantly down-regulated by CAV infection, suggesting potential roles for these genes as regulators of viral infection or cell defence. These results extend our understanding of CAV-induced immunosuppression and suggest a global immune dysregulation following CAV infection.

No MeSH data available.


Related in: MedlinePlus

T-cell receptor signalling was the most significant gene network of over-expressed genes in infected samples of thymus as identified by Ingenuity Pathway Analysis (www.ingenuity.com).Colored nodes represent differentially regulated genes (Table 4) while genes in uncolored nodes were not identified as differentially expressed and were integrated into the computationally generated network indicating a relevance to it (S1 File). T-cell receptor signalling gene relationships were overlaid to the network. Solid interconnecting lines represent genes directly connected and dotted lines signify the indirect connection between genes and cellular functions. Top functions of the genes were related to T-cell receptor signalling, immune response and cellular assembly and death, identified around the MALT1 gene (in red). Node shapes represent different biological molecules.
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pone.0134866.g002: T-cell receptor signalling was the most significant gene network of over-expressed genes in infected samples of thymus as identified by Ingenuity Pathway Analysis (www.ingenuity.com).Colored nodes represent differentially regulated genes (Table 4) while genes in uncolored nodes were not identified as differentially expressed and were integrated into the computationally generated network indicating a relevance to it (S1 File). T-cell receptor signalling gene relationships were overlaid to the network. Solid interconnecting lines represent genes directly connected and dotted lines signify the indirect connection between genes and cellular functions. Top functions of the genes were related to T-cell receptor signalling, immune response and cellular assembly and death, identified around the MALT1 gene (in red). Node shapes represent different biological molecules.

Mentions: The most significant CAV-induced gene expression changes were observed in the thymus. Analysis of expressed genes in the thymus samples of CAV-infected chickens by IPA identified four gene networks of differentially regulated genes. Gene networks are algorithmically generated based on their connectivity and ranked based upon a score (S1 File). Fig 2 shows the most significant gene network (Score = 33), focused on TCR signalling relationships between differentially regulated genes.


Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.

Giotis ES, Rothwell L, Scott A, Hu T, Talbot R, Todd D, Burt DW, Glass EJ, Kaiser P - PLoS ONE (2015)

T-cell receptor signalling was the most significant gene network of over-expressed genes in infected samples of thymus as identified by Ingenuity Pathway Analysis (www.ingenuity.com).Colored nodes represent differentially regulated genes (Table 4) while genes in uncolored nodes were not identified as differentially expressed and were integrated into the computationally generated network indicating a relevance to it (S1 File). T-cell receptor signalling gene relationships were overlaid to the network. Solid interconnecting lines represent genes directly connected and dotted lines signify the indirect connection between genes and cellular functions. Top functions of the genes were related to T-cell receptor signalling, immune response and cellular assembly and death, identified around the MALT1 gene (in red). Node shapes represent different biological molecules.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526643&req=5

pone.0134866.g002: T-cell receptor signalling was the most significant gene network of over-expressed genes in infected samples of thymus as identified by Ingenuity Pathway Analysis (www.ingenuity.com).Colored nodes represent differentially regulated genes (Table 4) while genes in uncolored nodes were not identified as differentially expressed and were integrated into the computationally generated network indicating a relevance to it (S1 File). T-cell receptor signalling gene relationships were overlaid to the network. Solid interconnecting lines represent genes directly connected and dotted lines signify the indirect connection between genes and cellular functions. Top functions of the genes were related to T-cell receptor signalling, immune response and cellular assembly and death, identified around the MALT1 gene (in red). Node shapes represent different biological molecules.
Mentions: The most significant CAV-induced gene expression changes were observed in the thymus. Analysis of expressed genes in the thymus samples of CAV-infected chickens by IPA identified four gene networks of differentially regulated genes. Gene networks are algorithmically generated based on their connectivity and ranked based upon a score (S1 File). Fig 2 shows the most significant gene network (Score = 33), focused on TCR signalling relationships between differentially regulated genes.

Bottom Line: The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR.Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow.From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Agri-Food and Biosciences Institute, Belfast, United Kingdom; Queen's University Belfast, Belfast, United Kingdom; The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
Chicken Anaemia Virus (CAV) is an economically important virus that targets lymphoid and erythroblastoid progenitor cells leading to immunosuppression. This study aimed to investigate the interplay between viral infection and the host's immune response to better understand the pathways that lead to CAV-induced immunosuppression. To mimic vertical transmission of CAV in the absence of maternally-derived antibody, day-old chicks were infected and their responses measured at various time-points post-infection by qRT-PCR and gene expression microarrays. The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR. The global gene expression profiles of mock-infected (control) and CAV-infected chickens at 14 dpi were also compared using a chicken immune-related 5K microarray. Although in the thymus there was evidence of induction of an innate immune response following CAV infection, this was limited in magnitude. There was little evidence of a Th1 adaptive immune response in any lymphoid tissue, as would normally be expected in response to viral infection. Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow. From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis. Expression levels of a number of adaptor proteins, such as src-like adaptor protein (SLA), a negative regulator of T-cell receptor signalling and the transcription factor Special AT-rich Binding Protein 1 (SATB1), were significantly down-regulated by CAV infection, suggesting potential roles for these genes as regulators of viral infection or cell defence. These results extend our understanding of CAV-induced immunosuppression and suggest a global immune dysregulation following CAV infection.

No MeSH data available.


Related in: MedlinePlus